Methods and devices for monitoring myocardial mechanical stability

ABSTRACT

Embodiments of the present invention relate to implantable systems, and methods for use therewith, for monitoring myocardial mechanical stability based on a signal that is indicative of mechanical functioning of a patient&#39;s heart for a plurality of consecutive beats. Certain embodiments use time domain techniques, while other embodiments use frequency domain techniques, to monitor myocardial mechanical stability. In certain embodiments the patient&#39;s heart is paced using a patterned pacing sequence that repeats every N beats. In other embodiments, the patient&#39;s heart need not be paced. This abstract is not intended to be a complete description of, or limit the scope of, the invention.

PRIORITY CLAIM

This application is a divisional of, and claims priority to U.S. patentapplication Ser. No. 11/421,915 (Attorney Docket No. A06P3010), filedJun. 2, 2006, entitled “METHODS AND DEVICES FOR MONITORING MYOCARDIALMECHANICAL STABILITY,” which is incorporated herein by reference.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application relates to the following patent applications,which are incorporated herein by reference: U.S. patent application Ser.No. 11/354,629, entitled “Time Domain Monitoring of MyocardialElectrical Stability,” (Attorney Docket No. A06P3003-US1), filed Feb.14, 2006; and U.S. patent application Ser. No. 11/354,732, entitled“Frequency Domain Monitoring of Myocardial Electrical Stability,”(Attorney Docket No. A06P3003-US2), filed Feb. 14, 2006.

FIELD OF THE INVENTION

The present invention generally relates methods and devices that arecapable of monitoring myocardial mechanical stability, includingdetecting mechanical alternans patterns.

BACKGROUND

Mechanical alternans, also known as mechanical pulse alternans (MPA),relate to the situation where alternating contractions of the heartexhibit alternating values of contraction force or magnitude that causeejected blood to exhibit similar alternating values of diastolicpressure amplitude. More specifically, the presence of mechanicalalternans can be defined by a consistent alternation in peak leftventricular (LV) pressure, or dP/dt, in successive beats.

Visible mechanical alternans have been observed in patients with severecongestive heart failure caused by global left ventricular dysfunction,and is considered to be a terminal sign in this population. Mechanicalalternans is characterized by alternating strong and weak beats with asubstantially constant beat-to-beat interval. Although its preciseorigin remains unclear, studies have suggested a link to abnormalintracellular Ca2+ cycling in failing cardiomyocytes. Studies have alsoshown that prevalence of mechanical alternans increases with exerciseand dobutamine loading compared to rest, indicating that mechanicalalternan is a rate dependent phenomenon. Accordingly, it is believedthat it would be useful to provide methods and systems for chronicallymonitoring for mechanical alternans, and more generally, monitoringmyocardial electrical stability.

BRIEF SUMMARY OF THE INVENTION

Embodiments of the present invention relate to implantable systems, andmethods for use therewith, for monitoring myocardial mechanicalstability. In accordance with an embodiment, a signal is obtained thatis indicative of mechanical functioning of the patient's heart for aplurality of consecutive beats, and a metric of the signal is determinedfor each of the plurality of consecutive beats. The signal that isindicative of the mechanical function of the patient's heart can beobtained using one or more implanted sensor. In one embodiment, thesensor is a pressure transducer that obtains measures of ventricularpressure. In another embodiment, the sensor is an accelerometer thatobtains measures of contraction strength. In a further embodiment, thesensor is a blood flow transducer that obtains measures of blood flowrate. In still another embodiment, the sensor is an acoustic transducerthat obtains measures of heart sounds. Such an acoustic transducer canbe, e.g., a microphone or an accelerometer that responds to acousticvibrations transmitted through body fluids, to thereby detectalternating loud and soft sounds. In a further embodiment, the sensor isan impedance measuring circuit having voltage sense electrodes tomeasure volumetric alternans, which is a surrogate of mechanicalalternans. In still another embodiment, the sensor is aphoto-plethysmography (PPG) sensor. In a further embodiment, the sensoris an SVO2 sensor. These are just some examples of sensors that arecapable of measuring the mechanical functioning of the heart, or asurrogate thereof, in accordance with embodiments of the presentinvention. Other types of sensors capable of measuring the mechanicalfunctioning of the heart, or a surrogate thereof, are also within thescope of the present invention.

The plurality of consecutive beats is divided into a plurality of setsof N consecutive beats, wherein N is an integer that is at least 2. Inspecific embodiments, N is an integer that is at least 3. Then, for eachof the plurality of sets of N consecutive beats, one or more pairwisecombination of the metrics is determined for consecutive pairs of beats.Corresponding pairwise combinations, determined for the plurality ofsets of N consecutive beats, are cumulative averaged or cumulativesummed to thereby produce a plurality of cumulative values. Myocardialmechanical stability is monitored based on the cumulative values, e.g.,by determining whether mechanical alternans are present. In accordancewith a specific embodiment, myocardial mechanical stability is trackedby repeating the above steps over time.

In accordance with an embodiment, the patient's heart is paced for aperiod of time using a patterned pacing sequence that repeats every Nbeats, and the signal indicative of mechanical functioning of thepatient's heart is obtained while the patient's heart is being pacedusing the patterned pacing sequence.

In accordance with an embodiment, corresponding pairwise differences arecumulative averaged to produce the plurality of cumulative values, andmechanical alternans are determined to be present when the cumulativevalues exceed a specified threshold.

In accordance with another embodiment, corresponding pairwisedifferences are cumulative summed to produce the plurality of cumulativevalues, and mechanical alternans are determined to be present when aslope of the cumulative values exceeds a specified slope threshold.

In accordance with an embodiment, the pairwise combinations are boundedprior to the cumulative averaging or cumulative summing.

In accordance with certain embodiments, disruptive beats are detected,if they exist, based on the cumulative values. This way the disruptivebeats can be compensated for. In a specific embodiment, wherecorresponding pairwise differences are cumulative summed to determinethe plurality of cumulative values, a disruptive beat is detected if thecumulative values continually stay within a range and then suddenly gooutside the range and continually stay within a further range. Inanother embodiment, where corresponding pairwise differences arecumulative summed to produce the plurality of cumulative values, adisruptive beat is detected if the cumulative values continuallyincrease and then suddenly continually decrease.

The above described embodiments relate to monitoring myocardialmechanical stability using time domain data and time domain techniques.Further embodiments, summarized below, convert time domain data tofrequency domain data, so that frequency domain techniques can be usedfor monitoring myocardial mechanical stability.

In accordance with specific embodiments of the present invention, an Nbeat alternans pattern can be detected from a signal that is indicativeof mechanical functioning of the patient's heart for a plurality ofconsecutive beats, where N is an integer that is at least 3. This can beaccomplished by dividing the plurality of consecutive beats into aplurality of sets of N consecutive beats, and for each set of Nconsecutive beats, selecting 2 of the N beats to produce a sub-set of 2beats per set of N consecutive beats. For example, in a specificembodiment, the first 2 beats from each set of N beats are selected.

Time domain data, associated with the plurality of sub-sets of 2 beats,is transformed to frequency domain data. Then, there is a determination,based on the frequency domain data, of the patient's myocardialmechanical stability. In specific embodiments the alternans magnitude at0.5 cycles/beat is determined based on the frequency domain data, andmyocardial mechanical stability is monitored based on the alternansmagnitude at 0.5 cycles/beat. This can include, for example,determining, based on the alternans magnitude at 0.5 cycles/beat,whether mechanical alternans are present. In accordance with anembodiment, changes in the alternans magnitude at 0.5 cycles/beat istracked over time to thereby track changes in myocardial mechanicalstability.

In accordance with an embodiment, the patient's heart is paced for aperiod of time using a patterned pacing sequence that repeats every Nbeats, and the signal indicative of mechanical functioning of thepatient's heart if obtained while the patient's heart is being pacedusing the patterned pacing sequence.

This description is not intended to be a complete description of, orlimit the scope of, the invention. Other features, aspects, and objectsof the invention can be obtained from a review of the specification, thefigures, and the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a simplified diagram illustrating an exemplary ICD inelectrical communication with a patient's heart.

FIG. 2 is a functional block diagram of an exemplary ICD that canprovide cardioversion, defibrillation, and pacing stimulation in fourchambers of a heart, and detect the presence of mechanical alternans, inaccordance with embodiments of the present invention.

FIG. 3 is a high-level flow diagram that is useful for describingembodiments of the present invention that are used to monitor myocardialmechanical stability.

FIG. 4 is a high-level flow diagram that is useful for describing timedomain embodiments of the present invention.

FIG. 5 is a graph that is useful for describing how pairwisecombinations can be bound, in accordance with embodiments of the presentinvention.

FIGS. 6A and 6B are graphs that are useful for describing how ofcumulative average values can be used to detect the presence ofmechanical alternans, in accordance with embodiments of the presentinvention.

FIGS. 7A and 7B are graphs that are useful for describing how ofcumulative sum values can be used to detect the presence of mechanicalalternans, in accordance with embodiments of the present invention.

FIG. 8A is a graph that is useful for describing how cumulative averagevalues can be used to detect disruptive beats, in accordance withembodiments of the present invention.

FIG. 8B is a graph that is useful for describing how cumulative sumvalues can be used to detect disruptive beats, in accordance withembodiments of the present invention.

FIG. 9 is a high-level flow diagram that is useful for describingfrequency domain embodiments of the present invention.

FIG. 10 is a graph that is useful for describing how a Fourier Transformor Fast Fourier Transform can be performed on time domain data.

FIG. 11 is an exemplary alternans magnitude versus frequency graph for apatient paced using a patterned pacing sequence that repeats every 4beats, where the frequency of interest is 0.25 cycles/beat.

FIG. 12 is an exemplary alternans magnitude versus frequency graphproduced starting with the same time domain data used to produce FIG.11, but using the embodiment of the present invention described withreference to FIG. 9, with the frequency of interest being 0.5cycles/beat.

DETAILED DESCRIPTION OF THE INVENTION

The following detailed description of the present invention refers tothe accompanying drawings that illustrate exemplary embodimentsconsistent with this invention. Other embodiments are possible, andmodifications may be made to the embodiments within the spirit and scopeof the present invention. Therefore, the following detailed descriptionis not meant to limit the invention. Rather, the scope of the inventionis defined by the appended claims.

It would be apparent to one of skill in the art that the presentinvention, as described below, may be implemented in many differentembodiments of hardware, software, firmware, and/or the entitiesillustrated in the figures. Any actual software and/or hardwaredescribed herein is not limiting of the present invention. Thus, theoperation and behavior of the present invention will be described withthe understanding that modifications and variations of the embodimentsare possible, given the level of detail presented herein.

Exemplary ICD

Before describing the invention in detail, it is helpful to describe anexample environment in which the invention may be implemented. Thepresent invention is particularly useful in the environment of animplantable cardiac device that can monitor mechanical activity of aheart and deliver appropriate electrical therapy, for example, pacingpulses, cardioverting and defibrillator pulses, and drug therapy, asrequired. Implantable cardiac devices include, for example, pacemakers,cardioverters, defibrillators, implantable cardioverter defibrillators,and the like. The term “implantable cardiac device” or simply “ICD” isused herein to refer to any implantable cardiac device. FIGS. 1 and 2illustrate such an environment in which embodiments of the presentinvention can be used.

Referring first to FIG. 1, an exemplary ICD 10 is shown in electricalcommunication with a patient's heart 12 by way of three leads, 20, 24and 30, suitable for delivering multi-chamber stimulation and pacingtherapy. To sense atrial cardiac signals and to provide right atrialchamber stimulation therapy, ICD 10 is coupled to implantable rightatrial lead 20 having at least an atrial tip electrode 22, whichtypically is implanted in the patient's right atrial appendage.

To sense left atrial and ventricular cardiac signals and to provideleft-chamber pacing therapy, ICD 10 is coupled to “coronary sinus” lead24 designed for placement in the “coronary sinus region” via thecoronary sinus for positioning a distal electrode adjacent to the leftventricle and/or additional electrode(s) adjacent to the left atrium. Asused herein, the phrase “coronary sinus region” refers to thevasculature of the left ventricle, including any portion of the coronarysinus, great cardiac vein, left marginal vein, left posteriorventricular vein, middle cardiac vein, and/or small cardiac vein or anyother cardiac vein accessible by the coronary sinus.

Accordingly, exemplary coronary sinus lead 24 is designed to receiveatrial and ventricular cardiac signals and to deliver left ventricularpacing therapy using at least a left ventricular tip electrode 26, leftatrial pacing therapy using at least a left atrial ring electrode 27,and shocking therapy using at least a left atrial coil electrode 28.

ICD 10 is also shown in electrical communication with the patient'sheart 12 by way of an implantable right ventricular lead 30 having, inthis embodiment, a right ventricular tip electrode 32, a rightventricular ring electrode 34, a right ventricular (RV) coil electrode36, and a superior vena cava (SVC) coil electrode 38. Typically, rightventricular lead 30 is transvenously inserted into heart 12 so as toplace the right ventricular tip electrode 32 in the right ventricularapex so that RV coil electrode 36 will be positioned in the rightventricle and SVC coil electrode 38 will be positioned in the SVC.Accordingly, right ventricular lead 30 is capable of receiving cardiacsignals and delivering stimulation in the form of pacing and shocktherapy to the right ventricle.

In FIG. 1, ICD 10 is also shown as being in electrical communicationwith the patient's heart 12 by way of a vagal stimulation lead 25,having, e.g., three vagal stimulation electrodes 31, 33, and 35 capableof delivering stimulation bursts to the patient's vagus nerve.Alternatively, vagal stimulation electrodes 31, 33, and 35 can bepositioned in the epicardial fat pad near the sinoatrial (SA) node.Based on the description herein, one skilled in the relevant art(s) willunderstand that the invention can be implemented by positioning vagalstimulation electrodes 31, 33, and 35 in alternate locations, such as inproximity to the cervical vagus, or implanted near or inside the SVC,the inferior vena cava (IVC), or the coronary sinus (CS), where they arealso capable of delivering stimulation bursts to the patient's vagusnerve.

One of the above described leads (or a further lead) can also connect afurther sensor (not specifically shown in FIG. 1, but shown as sensor 14in FIG. 2) to the ICD 10, where the further sensor 14 is capable ofmeasuring the mechanical functioning of the heart, or a surrogatethereof. In one embodiment, the sensor 14 is a pressure transducer thatobtains measures of ventricular pressure. In another embodiment, thesensor 14 is an accelerometer that obtains measures of contractionstrength. In a further embodiment, the sensor 14 is a blood flowtransducer that obtains measures of blood flow rate. In still anotherembodiment, the sensor 14 is an acoustic transducer that obtainsmeasures of heart sounds. Such an acoustic transducer can be, e.g., amicrophone or an accelerometer that responds to acoustic vibrationstransmitted through body fluids, to thereby detect alternating loud andsoft sounds. In a further embodiment, the sensor 14 is an impedancemeasuring circuit having voltage sense electrodes to measure volumetricalternans, which is a surrogate of mechanical alternans. In stillanother embodiment, the sensor 14 is a photo-plethysmography (PPG)sensor that measure pulse pressure. In a further embodiment, the sensoris a venous oxygen saturation (SVO2) sensor that measures venous oxygensaturation levels, which are believed to be indicative of mechanicalfunctioning of the heart. These are just some examples of sensors thatare capable of measuring the mechanical functioning of the heart, or asurrogate thereof. Other types of sensors capable of measuring themechanical functioning of the heart, or a surrogate thereof, are alsowithin the scope of the present invention.

FIG. 2 shows a simplified block diagram of ICD 10, which is capable oftreating both fast and slow arrhythmias with stimulation therapy,including cardioversion, defibrillation, and pacing stimulation. While aparticular multi-chamber device is shown, it is shown for illustrationpurposes only, and one of skill in the art could readily duplicate,eliminate or disable the appropriate circuitry in any desiredcombination to provide a device capable of treating the appropriatechamber(s) with the desired cardioversion, defibrillation and pacingstimulation.

A housing 40 of ICD 10, shown schematically in FIG. 2, is often referredto as the “can,” “case” or “case electrode” and may be programmablyselected to act as the return electrode for all “unipolar” modes.Housing 40 may further be used as a return electrode alone or incombination with one or more of coil electrodes, 28, 36, and 38 forshocking purposes. Housing 40 further includes a connector (not shown)having a plurality of terminals, 42, 44, 46, 48, 52, 54, 56, 58, 218,219 and 220 (shown schematically and, for convenience, the names of theelectrodes to which they are connected are shown next to the terminals).As such, to achieve right atrial sensing and pacing, the connectorincludes at least a right atrial tip terminal (AR TIP) 42 adapted forconnection to atrial tip electrode 22.

To achieve left chamber sensing, pacing and shocking, the connectorincludes at least a left ventricular tip terminal (VL TIP) 44, a leftatrial ring terminal (AL RING) 46, and a left atrial shocking terminal(AL COIL) 48, which are adapted for connection to left ventricular ringelectrode 26, left atrial tip electrode 27, and left atrial coilelectrode 28, respectively.

To support right chamber sensing, pacing, and shocking the connectoralso includes a right ventricular tip terminal (VR TIP) 52, a rightventricular ring terminal (VR RING) 54, a right ventricular shockingterminal (RV COIL) 56, and an SVC shocking terminal (SVC COIL) 58, whichare configured for connection to right ventricular tip electrode 32,right ventricular ring electrode 34, RV coil electrode 36, and SVC coilelectrode 38, respectively.

The connector is also shown as including vagal lead terminals (VAGALELECTRODES) 218, 219, and 220, which are configured for connection tovagal stimulation electrodes 31, 33, and 35, respectively, to supportthe delivery of vagal stimulation bursts. Additionally, where the sensor14 is connected to the ICD by its own lead, the connector can include aterminal 222, which is configured for connecting the sensor 14 to theICD. It is also possible that the sensor 14 is integrated with thehousing 40, and thus does not need to be connected via a terminal.

At the core of ICD 10 is a programmable microcontroller 60, whichcontrols the various modes of stimulation therapy. As is well known inthe art, microcontroller 60 typically includes one or moremicroprocessor, or equivalent control circuitry, designed specificallyfor controlling the delivery of stimulation therapy and can furtherinclude RAM or ROM memory, logic and timing circuitry, state machinecircuitry, and I/O circuitry. Typically, microcontroller 60 includes theability to process or monitor input signals (data) as controlled by aprogram code stored in a designated block of memory. The details of thedesign of microcontroller 60 are not critical to the present invention.Rather, any suitable microcontroller 60 can be used to carry out thefunctions described herein. The use of microprocessor-based controlcircuits for performing timing and data analysis functions are wellknown in the art.

Representative types of control circuitry that may be used with theinvention include the microprocessor-based control system of U.S. Pat.No. 4,940,052 (Mann et. al.) and the state-machines of U.S. Pat. Nos.4,712,555 (Sholder) and 4,944,298 (Sholder). For a more detaileddescription of the various timing intervals used within the ICD's andtheir inter-relationship, see U.S. Pat. No. 4,788,980 (Mann et. al.).The '052, '555, '298 and '980 patents are incorporated herein byreference.

As shown in FIG. 2, an atrial pulse generator 70 and a ventricular pulsegenerator 72 generate pacing stimulation pulses for delivery by rightatrial lead 20, right ventricular lead 30, and/or coronary sinus lead 24via an electrode configuration switch 74. It is understood that in orderto provide stimulation therapy in each of the four chambers of theheart, atrial and ventricular pulse generators 70 and 72 may includededicated, independent pulse generators, multiplexed pulse generators,or shared pulse generators. Pulse generators 70 and 72 are controlled bymicrocontroller 60 via appropriate control signals 71 and 78,respectively, to trigger or inhibit the stimulation pulses.

Also shown in FIG. 2, is a vagal pulse generator 214 that is controlledby vagal stimulation control 210 (within microcontroller 60) via acontrol signal 212, to trigger or inhibit the delivery of vagalstimulation pulses.

Microcontroller 60 further includes timing control circuitry 79, whichis used to control pacing parameters (e.g., the timing of stimulationpulses) as well as to keep track of the timing of refractory periods,PVARP intervals, noise detection windows, evoked response windows, alertintervals, marker channel timing, etc., which are well known in the art.Examples of pacing parameters include, but are not limited to,atrio-ventricular (AV) delay, interventricular (RV-LV) delay, atrialinterconduction (A-A) delay, ventricular interconduction (V-V) delay,and pacing rate.

Switch 74 includes a plurality of switches for connecting the desiredelectrodes to the appropriate I/O circuits, thereby providing completeelectrode programmability. Accordingly, switch 74, in response to acontrol signal 80 from microcontroller 60, determines the polarity ofthe stimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) byselectively closing the appropriate combination of switches (not shown)as is known in the art.

Atrial sensing circuits 82 and ventricular sensing circuits 84 may alsobe selectively coupled to right atrial lead 20, coronary sinus lead 24,and right ventricular lead 30, through switch 74 for detecting thepresence of cardiac activity in each of the four chambers of the heart.Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE)sensing circuits 82 and 84 may include dedicated sense amplifiers,multiplexed amplifiers, or shared amplifiers. Switch 74 determines the“sensing polarity” of the cardiac signal by selectively closing theappropriate switches, as is also known in the art. In this way, aclinician may program the sensing polarity independent of thestimulation polarity.

Each sensing circuit, 82 and 84, preferably employs one or more lowpower, precision amplifiers with programmable gain and/or automatic gaincontrol, bandpass filtering, and a threshold detection circuit, as knownin the art, to selectively sense the cardiac signal of interest. Theautomatic gain control enables ICD 10 to deal effectively with thedifficult problem of sensing the low amplitude signal characteristics ofatrial or ventricular fibrillation. Such sensing circuits, 82 and 84,can be used to determine cardiac performance values used in the presentinvention.

The outputs of atrial and ventricular sensing circuits 82 and 84 areconnected to microcontroller 60 which, in turn, are able to trigger orinhibit atrial and ventricular pulse generators, 70 and 72,respectively, in a demand fashion in response to the absence or presenceof cardiac activity, in the appropriate chambers of the heart. Sensingcircuits 82 and 84, in turn, receive control signals over signal lines86 and 88 from microcontroller 60 for purposes of measuring cardiacperformance at appropriate times, and for controlling the gain,threshold, polarization charge removal circuitry (not shown), and timingof any blocking circuitry (not shown) coupled to the inputs of sensingcircuits 82 and 86.

For arrhythmia detection, ICD 10 utilizes the atrial and ventricularsensing circuits 82 and 84 to sense cardiac signals to determine whethera rhythm is physiologic or pathologic. The timing intervals betweensensed events (e.g., P-waves, R-waves, and depolarization signalsassociated with fibrillation are then classified by microcontroller 60by comparing them to a predefined rate zone limit (i.e., bradycardia,normal, low rate VT, high rate VT, and fibrillation rate zones) andvarious other characteristics (e.g., sudden onset, stability,physiologic sensors, and morphology, etc.) in order to determine thetype of remedial therapy that is needed (e.g., bradycardia pacing,anti-tachycardia pacing, cardioversion shocks or defibrillation shocks,collectively referred to as “tiered therapy”).

Microcontroller 60 utilizes arrhythmia detector 75 and morphologydetector 77 to recognize and classify arrhythmia so that appropriatetherapy can be delivered. The morphology detector 77 may also be used todetect signal morphologies that are useful for detecting mechanicalalternans, in accordance with embodiments of the present inventiondescribed below. The arrhythmia detector 75 and morphology detector 77can be implemented within the microcontroller 60, as shown in FIG. 2.Thus, these elements can be implemented by software, firmware, orcombinations thereof. It is also possible that all, or portions, ofthese detectors can be implemented using hardware.

Cardiac signals are also applied to the inputs of an analog-to-digital(A/D) data acquisition system 90. Data acquisition system 90 isconfigured to acquire intracardiac electrogram signals, convert the rawanalog data into a digital signal, and store the digital signals forlater processing and/or telemetric transmission to an external device102. Data acquisition system 90 is coupled to right atrial lead 20,coronary sinus lead 24, and right ventricular lead 30 through switch 74to sample cardiac signals across any pair of desired electrodes. Thedata acquisition system 90 (or a separate similar system) can alsoconvert analog signals received from the sensor(s) 14 into digitalsignals that can be monitored by the myocardial mechanical stabilitydetector 202 and/or stored in memory 94.

Data acquisition system 90 can be coupled to microcontroller 60, orother detection circuitry, for detecting an evoked response from heart12 in response to an applied stimulus, thereby aiding in the detectionof “capture.” Capture occurs when an electrical stimulus applied to theheart is of sufficient energy to depolarize the cardiac tissue, therebycausing the heart muscle to contract. Microcontroller 60 detects adepolarization signal during a window following a stimulation pulse, thepresence of which indicates that capture has occurred. Microcontroller60 enables capture detection by triggering ventricular pulse generator72 to generate a stimulation pulse, starting a capture detection windowusing timing control circuitry 79 within microcontroller 60, andenabling data acquisition system 90 via a control signal 92 to samplethe cardiac signal that falls in the capture detection window and, basedon the amplitude, determines if capture has occurred. Additionally,microcontroller 60 can detect cardiac events, such as prematurecontractions of ventricles, and the like.

The implementation of capture detection circuitry and algorithms arewell known. See for example, U.S. Pat. No. 4,729,376 (Decote, Jr.); U.S.Pat. No. 4,708,142 (Decote, Jr.); U.S. Pat. No. 4,686,988 (Sholder);U.S. Pat. No. 4,969,467 (Callaghan et. al.); and U.S. Pat. No. 5,350,410(Mann et. al.), which patents are hereby incorporated herein byreference. The type of capture detection system used is not critical tothe present invention.

Microcontroller 60 is further coupled to a memory 94 by a suitabledata/address bus 96, wherein the programmable operating parameters usedby microcontroller 60 are stored and modified, as required, in order tocustomize the operation of ICD 10 to suit the needs of a particularpatient. Such operating parameters define, for example, pacing pulseamplitude, pulse duration, electrode polarity, rate, sensitivity,automatic features, arrhythmia detection criteria, and the amplitude,waveshape and vector of each shocking pulse to be delivered to heart 12within each respective tier of therapy.

The operating parameters of ICD 10 may be non-invasively programmed intomemory 94 through telemetry circuit 100 in telemetric communication withexternal device 102, such as a programmer, transtelephonic transceiver,or a diagnostic system analyzer. Telemetry circuit 100 is activated bymicrocontroller 60 by a control signal 106. Telemetry circuit 100advantageously allows intracardiac electrograms and status informationrelating to the operation of ICD 10 (as contained in microcontroller 60or memory 94) to be sent to external device 102 through establishedcommunication link 104.

For examples of such devices, see U.S. Pat. No. 4,809,697, entitled“Interactive Programming and Diagnostic System for use with ImplantablePacemaker” (Causey, III et al.); U.S. Pat. No. 4,944,299, entitled “HighSpeed Digital Telemetry System for Implantable Device” (Silvian); andU.S. Pat. No. 6,275,734, entitled “Efficient Generation of SensingSignals in an Implantable Medical Device such as a Pacemaker or ICD”(McClure et al.), which patents are hereby incorporated herein byreference.

ICD 10 further includes a physiologic sensor 108 that can be used todetect changes in cardiac performance or changes in the physiologicalcondition of the heart. Accordingly, microcontroller 60 can respond byadjusting the various pacing parameters (such as rate, AV Delay, RV-LVDelay, V-V Delay, etc.). Microcontroller 60 controls adjustments ofpacing parameters by, for example, controlling the stimulation pulsesgenerated by the atrial and ventricular pulse generators 70 and 72.While shown as being included within ICD 10, it is to be understood thatphysiologic sensor 108 may also be external to ICD 10, yet still beimplanted within or carried by the patient. More specifically, sensor108 can be located inside ICD 10, on the surface of ICD 10, in a headerof ICD 10, or on a lead (which can be placed inside or outside thebloodstream).

Also shown in FIG. 2 is an activity sensor 116. The activity sensor 116(e.g., an accelerometer) can be used to determine the activity of thepatient. Such information can be used for rate responsive pacing, or, inaccordance with embodiments of the present invention, to determinewhether the patient is sufficiently at rest such that certain baselinemeasurements can be obtained. If the sensor 116 is a multi-dimensionalaccelerometer, then posture information can also be extracted. Thefollowing patents, which are incorporated herein by reference, describeexemplary activity sensors that can be used to detect activity of apatient (some also detect posture): U.S. Pat. No. 6,658,292 to Kroll etal., entitled “Detection of Patient's Position and Activity Status using3D Accelerometer-Based Position Sensor”; U.S. Pat. No. 6,466,821 toKroll et al., entitled “Orientation of Patient's Position Sensor usingExternal Field”; and U.S. Pat. No. 6,625,493 to Pianca et al., entitled“AC/DC Multi-Axis Accelerometer for Determining Patient Activity andBody Position.” Simple activity sensors employ a piezoelectric crystalor a cantilever beam having a film of a piezoelectric polymer adhered toa surface of the beam. These are just a few exemplary types of activitysensors 116, which are not meant to be limiting.

Also shown in FIG. 2 is the sensor 14 that is used to obtain a signalthat is indicative of mechanical functioning of a patient's heart. Asmentioned above, the sensor 14 can be: a pressure transducer thatobtains measures of ventricular pressure; an accelerometer that obtainsmeasures of contraction strength; a blood flow transducers that obtainsmeasures of blood flow rate; an acoustic transducer that obtainsmeasures of heart sounds; an impedance measuring circuit having voltagesense electrodes to measure volumetric alternans, which is a surrogateof mechanical alternans; a photo-plethysmography (PPG) sensor themeasures pulse pressure; or a venous oxygen saturation (SVO2) sensor.Exemplary acoustic transducers are disclosed in U.S. Pat. No. 6,527,729(Turcott), each of which is incorporated herein by reference. Exemplaryimplantable PPG sensors are disclosed in U.S. Pat. Nos. 6,409,675(Turcott) and 6,731,967 (Turcott), and U.S. patent application Ser. Nos.11/231,555 (Poore), filed Sep. 20, 2005, and 11/282,198 (Poore), filedNov. 17, 2005, each of which is incorporated herein by reference.Exemplary pressure transducers are disclosed in U.S. patent applicationSer. No. 11/072,942, filed Mar. 3, 2005 (Fayram et al.), which isincorporated herein by reference. These are just some examples ofsensors that are capable of measuring the mechanical functioning of theheart, or a surrogate thereof. Other types of sensors capable ofmeasuring the mechanical functioning of the heart, or a surrogatethereof, are also within the scope of the present invention.

The ICD 10 may also include a magnet detection circuitry (not shown),coupled to microcontroller 60. It is the purpose of the magnet detectioncircuitry to detect when a magnet is placed over ICD 10. A clinician mayuse the magnet to perform various test functions of ICD 10 and/or tosignal microcontroller 60 that the external programmer 102 is in placeto receive or transmit data to microcontroller 60 through telemetrycircuit 100.

As further shown in FIG. 2, ICD 10 can have an impedance measuringcircuit 112, which is enabled by microcontroller 60 via a control signal114. The known uses for an impedance measuring circuit 112 include, butare not limited to, lead impedance surveillance during the acute andchronic phases for proper lead positioning or dislodgement; detectingoperable electrodes and automatically switching to an operable pair ifdislodgement occurs; measuring respiration or minute ventilation;measuring thoracic impedance for determining shock thresholds; detectingwhen the device has been implanted; measuring stroke volume; anddetecting the opening of heart valves, etc. The impedance measuringcircuit 112 is advantageously coupled to switch 74 so that any desiredelectrode may be used. In the case where ICD 10 is intended to operateas a cardioverter, pacer or defibrillator, it must detect the occurrenceof an arrhythmia and automatically apply an appropriate electricaltherapy to the heart aimed at terminating the detected arrhythmia. Tothis end, microcontroller 60 further controls a shocking circuit 16 byway of a control signal 18. The shocking circuit 16 generates shockingpulses of low (up to about 0.5 Joules), moderate (about 0.5-10 Joules),or high energy (about 11 to 40 Joules), as controlled by microcontroller60. Such shocking pulses are applied to the patient's heart 12 throughat least two shocking electrodes (e.g., selected from left atrial coilelectrode 28, RV coil electrode 36, and SVC coil electrode 38). As notedabove, housing 40 may act as an active electrode in combination with RVelectrode 36, or as part of a split electrical vector using SVC coilelectrode 38 or left atrial coil electrode 28 (i.e., using the RVelectrode as a common electrode).

Cardioversion shocks are generally considered to be of low to moderateenergy level (so as to minimize pain felt by the patient), and/orsynchronized with an R-wave and/or pertaining to the treatment oftachycardia. Defibrillation shocks are generally of moderate to highenergy level (i.e., corresponding to thresholds in the range of about5-40 Joules), delivered asynchronously (since R-waves may be toodisorganized to be recognize), and pertaining exclusively to thetreatment of fibrillation. Accordingly, microcontroller 60 is capable ofcontrolling the synchronous or asynchronous delivery of the shockingpulses.

ICD 10 additionally includes a battery 110, which provides operatingpower to a load that includes all of the circuits shown in FIG. 2.

Mechanical Alternans

Still referring to FIG. 2, in accordance with embodiments of the presentinvention, the microcontroller 60 includes a myocardial mechanicalstability detector 202, which as described in more detail below, canmonitor myocardial mechanical stability, e.g., by detecting the presenceof mechanical alternans. The myocardial mechanical stability detector202 can be implemented within the microcontroller 60, as shown in FIG.2. Thus, myocardial mechanical stability detector 202 can be implementedby software, firmware, or combinations thereof. It is also possible thatall, or portions, of the myocardial mechanical stability detector 202can be implemented using hardware. Further, it is possible that all, orportions, of the myocardial mechanical stability detector 202 beimplemented external to the microcontroller 60.

In an embodiment, the myocardial mechanical stability detector 202triggers data acquisition circuit 90 and timing control circuit 79 toacquire a signal that is indicative of mechanical functioning of apatient's heart. Such a signal can be representative of an actualmeasure of mechanical functioning, or representative of a surrogate ofmechanical functions. For an example, such a signal, if obtained from apressure transducer within a ventricle, can be representative ofventricular pressure. In another embodiment, the signal isrepresentative of contraction strength, which can be obtained from anaccelerometer. In a further embodiment, the signal is representative ofblood flow rate, which can be obtained from a blood flow transducer. Inanother embodiment, the signal is representative of heart rate sounds,which can be obtained from a microphone or an accelerometer thatresponds to acoustic vibrations transmitted through body fluids. Instill another embodiment, the signal can representative of blood volume,which can be obtained using an impedance measuring circuit. In stillanother embodiment, the signal can be representative of pulse pressure,which can be obtained using a photo-plethysmography sensor. In stillanother embodiment, the signal can be representative of venous oxygensaturation (SVO2). Each of the above elements are exemplary sensors thatcan be used to acquire a signal that is representative of mechanicalfunctioning of a patient's heart, or a surrogate thereof. One ofordinary skill in the art, based on the disclosure herein, wouldunderstand that other types of sensors are also within the scope of thepresent invention.

Each of the above described signals are cyclical because they areindicative of the mechanical functioning of the heart, with each cycleof the signal corresponding to a beat of the patient's heart. Themyocardial mechanical stability detector 202 can measure metrics of eachcycle of the signal (i.e., metrics of each beat), to thereby determinewhether there is an alternation in such metrics. Examples of suchmetrics include, but are not limited to, amplitude, width, area, andmorphology. Depending on the signal being analyzed, the metrics can alsobe of specific portions or markers within the signal. The myocardialmechanical stability detector 202 can also trigger the implantabledevice 10 to respond appropriately when mechanical alternans aredetected, as will be explained in more detail below. Additionally, inconjunction with the telemetry circuit 100, the myocardial mechanicalstability detector 202 can be configured to deliver status information,relating to the patient's myocardial mechanical stability, to theexternal device 102 through an established communication link 104. Themyocardial mechanical stability detector 202 may also trigger a patientor physician alert in response to detecting mechanical alternans. Forexample, a patient alert 118, which produces a vibratory or auditoryalert, may be triggered by the myocardial mechanical stability detector202.

Electrical alternans, such as Twave alternans have been demonstrated inmany studies to be strong predictor of mortality, independent of leftventricular ejection fraction (LVEF). It had been generally believedthat an elevated constant heart rate is a requirement for the detectionof Twave alternans. However, a recent work published by Bulling a etal., entitled “Resonant Pacing Improves Twave Alternans Testing inPatients with Dilated Cardiomyopathy” (Heart Rhythm v1:S129, 2004)revealed a more robust detection with “resonant pacing” scheme. In thistechnique, Twave alternans with higher amplitudes were detected bypacing at a relatively shorter interval periodically once every fourthcycle during a moderately fast and constant pacing routine. This is anexample of a patterned pacing sequence that repeats every 4 beats. Otherexamples of patterned pacing sequences are disclosed in U.S. patentapplication Ser. No. 10/884,276 (Bullinga), filed Jan. 6, 2005,(Publication No. US 2005/0004608), entitled “System and Method forAssessment of Cardiac Electrophysiologic Stability and Modulation ofCardiac Oscillations,” which is incorporated herein by reference.Further examples of patterned pacing sequences are disclosed in U.S.patent application Ser. No. 11/341,086 (Farazi), filed Jan. 27, 2006,entitled “Pacing Schemes For Revealing Twave Alternans (TWA) at Low toModerate Heart Rates,” (Attorney Docket No. A05P3026), which is alsoincorporated herein by reference. The inventors of the present inventionbelieve that such patterned pacing will also reveal mechanical alternansat lower heart rates. Thus, in certain embodiments of the presentinvention, as will be described below, a patient is paced using apatterned pacing sequence that repeats every N beats, where N is aninteger. Some embodiments of the present invention can also be usedwhere the patient is paced using a constant elevated heart rate and/orwhen the patient is not paced at all.

By pacing a patient's heart with a patterned pacing sequence, theexpected alternans pattern is known. For example, if the patternedpacing sequence repeats every 3 beats, then it is expected that therewill be an ABCABCABC . . . alternans pattern; if the patterned pacingsequence repeats every 4 beats, then it is expected that there will bean ABCDABCDABCD . . . alternans pattern; and so on. In accordance withspecific embodiments of the present invention, because patterned pacingsequences are being used to induce specific expected mechanicalalternans patterns, analysis of the alternans can be optimized to matchthe pattern being induced.

Specific embodiments of the present invention will now be summarizedwith reference to the high level flow diagram of FIG. 3. In this flowdiagram, and the other flow diagrams described herein, the variousalgorithmic steps are summarized in individual “blocks”. Such blocksdescribe specific actions or decisions that are made or carried out asthe algorithm proceeds. Where a microcontroller (or equivalent) isemployed, the flow diagrams presented herein provide the basis for a“control program” that may be used by such a microcontroller (orequivalent) to effectuate the desired control of the cardiac device.Those skilled in the art may readily write such a control program basedon the flow diagrams and other descriptions presented herein. The stepsof the flow diagram can be implemented, e.g., by an implantable cardiacdevice, such as but not limited to ICD 10. It is also possible thatcertain steps can be implemented by a non-implantable device.

At step 300, a patient's heart is paced for a period of time using apatterned pacing sequence that repeats every N beats, where N is aninteger that is at least 2. In specific embodiments, N is at least 3.The term patterned pacing sequence as used herein refers to a repeatablepacing sequence where at least one paced beat's cycle length differsfrom another paced beat's cycle length. For example, assuming N=4, thepatterned pacing sequence used to pace the patient's heart can include 3consecutive beats having a baseline cycle length (CL) followed by ashortened beat (i.e., CL−Δt). In another example, also assuming N=4, thepatterned pacing sequence can include 3 consecutive beats having abaseline cycle length (CL) followed by a lengthened beat (i.e., CL+Δt).In another example where N=4, the patterned pacing sequence can includesuccessively shortened beats (e.g., CL, CL−Δt, CL−2Δt and CL−3Δt). Theseare just a few examples of patterned pacing sequences, which are notmeant to be limiting. Other example are provided in the patentapplications which were incorporated by reference above. To ensurecapture, each beat of the patterned pacing sequence should be shorterthan an intrinsic beat. Additionally, where the patient is normallypaced, each paced beat of a patterned pacing sequence should be shorterthan a beat length corresponding to the patient's normal pacing. Inaccordance with an embodiment, the pacing performed at step 300 isperformed by an implantable cardiac device (e.g., ICD 10).

At step 302, a signal is obtain that is indicative of mechanicalfunctioning of the patient's heart for a plurality of consecutive beatswhile the patient's heart is being paced using the patterned pacingsequence that repeats every N beats. Such a signal can be representativeof an actual measure of mechanical functioning, or representative of asurrogate of mechanical functions. In accordance with an embodiment, thesignal is representative of ventricular pressure, and is obtained from apressure transducer within a ventricle. In another embodiment, thesignal is representative of contraction strength and is obtained from anaccelerometer. In a further embodiment, the signal is representative ofblood flow rate and is obtained from a blood flow transducer. In anotherembodiment, the signal is representative of heart rate sounds and isobtained from a microphone or an accelerometer that responds to acousticvibrations transmitted through body fluids. In still another embodiment,the signal is representative of blood volume and is obtained using animpedance measuring circuit. In still another embodiment, the signal isrepresentative of pulse pressure and is obtained using aphoto-plethysmography sensor. In another embodiment, the signal isrepresentative of venous oxygen saturation and is obtained using an SVO2sensor. Each of the above elements are exemplary sensors that can beused to acquire a signal that is indicative of mechanical functioning ofa patient's heart. One of ordinary skill in the art, based on thedisclosure herein, would understand that other types signals obtainedfrom other types of sensors are also within the scope of the presentinvention. In accordance with an embodiment, data indicative of thesignal is stored within the ICD 10 (e.g., in memory 94).

At an optional step 304, the signal obtained at step 302 is cleaned up.This can be accomplished, e.g., by filtering the signal (or dataindicative of the signal) and/or removing noisy cycle segments of thesignal. Filtering the signal could include, e.g., the use of a low-passfilter with a cutoff frequency of about 250 Hz. Additionally, ahigh-pass filter can be used to reduce the contribution of DC-offsetsand respiration drift to the signal. Removal of noisy cycles can beaccomplished, e.g., by removing any number of cycles that are exposed tosevere noise, e.g., from myopotentials or electromagnetic interference.A further optional step is to resample stored cycles of the signal tomatch in length. For example, if a signal were originally sampled at 256Hz, it could be upsampled to 1000 Hz, stretched or compressed to match amean cycle length, and then down-sampled again to 256 Hz. The abovedescribed pre-processing to clean up the signal generally helps tominimize noise in the signal. Step 304 can also include removing easilydetected ectopic beats (e.g., premature contractions of the ventricles).For example, this can be accomplished by comparing each cardiac lengthto a mean cardiac length. An ectopic beat can then be identified where alength of a beat is less than a threshold percentage (e.g., 80%) of themean length, yet is surrounded by beats having lengths that are greaterthan the threshold percentage.

At step 306, a metric of the signal is determined for each of theplurality of consecutive beats. As explained above, the metric can beinclude maximum amplitude, peak-to-peak amplitude, width, area,morphology, or the like. At step 308, the plurality of consecutive beats(of the signal obtained at step 302, and optionally cleaned up at step304) are divided into a plurality of sets of N consecutive beats. For anexample, which is not meant to be limiting, assume the obtained signalis representative of 1000 beats, and N=4 (as in the examples discussedabove), then step 308 would include dividing the 1000 beats into 250sets of 4 consecutive beats. The order of certain steps is notimportant, unless a certain step is using the results of an earlierstep. For example, step 306 can be performed before, after, or at thesame time as step 308.

At a next step 310, a patients' myocardial mechanical stability ismonitored based on the plurality of sets of N consecutive beats. Suchmonitoring can be performed in the time domain, as discussed withreference to the FIG. 4, or in the frequency domain, as discussed withreference to FIG. 9.

At an optional step 312, an appropriate response can be trigger. Forexample, if it is determined at step 310 that an alternans magnitude isbeyond a threshold, then an appropriate response can be triggered. Forcompleteness, exemplary responses are discussed below.

Time Domain Analysis

One way to monitor a patient's myocardial mechanical stability (e.g., todetermine if mechanical alternans are present), in the time domain,based on the plurality of sets of N consecutive beats, is to simplyaverage metrics of corresponding beats from each set. A determination ofmyocardial mechanical stability (e.g., whether mechanical alternans arepresent) can then be made based on the averaged metrics. For example,assume that the desire is to determine whether mechanical alternans arepresent based on 250 sets of 4 consecutive beats (i.e., each setincludes a beat pattern ABCD). Also assume that the metric beingmeasured for each cycle of the signal (which corresponds to a beat) ismaximum amplitude. The maximum amplitudes of each of the 250 “A”cycles/beats can be averaged, the maximum amplitudes of each of the 250“B” cycles/beats can be averages, the maximum amplitudes of each of the250 “C” cycles/beats can be averaged, and the maximum amplitudes of eachof the 250 “D” cycles/beats can be averaged, resulting in averagemaximum amplitudes for cycles/beats ABCD. A difference between theaverage “A” maximum amplitude and the average “B” maximum amplitude canthen be determined, as can the difference between the average “B”maximum amplitude and the average “C” maximum amplitude, and thedifference between the average “C” maximum amplitude and the average “D”maximum amplitude. A determination of whether mechanical alternans arepresent can then be based on whether such differences exceedcorresponding thresholds. A potential problem with performing theaveraging suggested above is that such averaging may mask or buryimportant information included within the sets of N consecutive beats.For example, if there is a phase reversal, an ectopic beat, or anothertype of disruptive beat within one of the sets, the averaging assuggested above may mask such information. Additionally, large noiseartifacts may corrupt the results of such averaging.

FIG. 4 is a high level flow diagram useful for describing embodiments ofthe present invention that relate to monitoring myocardial mechanicalstability at step 310, in the time domain, based on the plurality ofsets of N consecutive beats produced at step 308.

Referring to FIG. 4, at step 402 one or more pairwise combination of themetrics for consecutive pairs of beats are determined for each of theplurality of sets of N consecutive beats. For example, assuming thatN=4, and thus, that each set of N consecutive beats includes beats A, B,C and D (i.e., beat pattern ABCD), then pairwise combinations can beproduced for beat pair AB, beat pair BC and/or beat pair CD. Forsimplicity, it will be assumed that pairwise combinations are producedonly for beat pair AB, for each set of 4 consecutive beats.

In accordance with an embodiment of the present invention, each pairwisecombination determined at step 402 is a pairwise difference. In otherwords, the pairwise combination for beat pair AB (referred to as S_(AB))is equal to a metric of beat A minus a corresponding metric of beat B(i.e., S_(AB)=metric A−metric B). For simplicity, it will be assumedthat the metric being used is maximum amplitude of a beat cycle. Thus,an exemplary pairwise combination for beat pair AB is equal to theamplitude of beat A minus the amplitude of beat B (i.e.,S_(AB)=amplitude (A)−amplitude (B)). Continuing with the example that1000 beats are separated into 250 sets of 4 consecutive beats, this willresult in 250 S_(AB) values (e.g., S_(AB1)=amplitude (A₁)−amplitude(B₁); S_(AB2)=amplitude (A₂)−amplitude (B₂); S_(AB3)=amplitude(A₃)−amplitude (B₃), etc.). If pairwise combinations are also producedfor beat pair BC and/or beat pair CD, then there would also be 250S_(BC) values (e.g., S_(BC1)=amplitude (B₁)−amplitude (C₁);S_(BC2)=amplitude (B₂)−amplitude (C₂); S_(BC3)=amplitude (B₃)−amplitude(C₃), etc.) and/or 250 S_(CD) values (e.g., S_(CD1)=amplitude(C₁)−amplitude (D₁); S_(CD2)=amplitude (C₂)−amplitude (D₂);S_(CD3)=amplitude (C₃)−amplitude (D₃), etc.).

In accordance with another embodiment of the present invention, eachpairwise combination determined at step 402 is a pairwise summation. Inother words, the pairwise combination for beat pair AB (referred to asS_(AB)) is equal to a metric of beat A plus a corresponding metric ofbeat B (i.e., S_(AB)=metric A+metric B). In still another embodiment ofthe present invention, each pairwise combination determined at step 402is a pairwise average. In other words, the pairwise combination for beatpair AB (referred to as S_(AB)) is equal to an average of a metric ofbeat A and a metric of beat B (i.e., S_(AB)=avg (metric A+metric B)).These are just a few examples of pairwise combinations. Other types ofpairwise combinations are also within the scope of the presentinvention.

A next step 404, which is optional, but preferred, is to bound thepairwise combinations produced at step 402, to minimize the effect oflarge noise artifacts. An example of this is shown in FIG. 5, wherepairwise differences are limited by an upper bound=6, and a lowerbound=4. The precise bound values can be determined, e.g., throughexperimentation. The bound values can be specific to a patient, orspecific to a population.

Returning to FIG. 4, at step 406, corresponding pairwise combinations(determined for the plurality of sets of N consecutive beats) arecumulative averaged or cumulative summed to thereby produce a pluralityof cumulative values (G). For example, where the pairwise combinationsare cumulative averaged, then the cumulative values G_(n)=avg (S₁+S₂ . .. +S_(n)). For a more specific example, G_(AB1)=S_(AB1); G_(AB2)=avg(S_(AB1)+S_(AB2)); G_(AB3)=avg (S_(AB1)+S_(AB2)+S_(AB3)); . . . andG_(ABn)=avg (S_(AB1)+S_(AB2)+S_(AB3) . . . +S_(ABn)). Where the pairwisecombinations are cumulative sums, then the cumulative values G_(n)=sum(S₁+S₂ . . . +S_(n)), e.g., G_(AB1)=S_(AB1); G_(AB2)=sum(S_(AB1)+S_(AB2)); G_(AB3)=sum (S_(AB1)+S_(AB2)+S_(AB3)); . . . andG_(ABn)=sum (S_(AB1)+S_(AB2)+S_(AB3) . . . +S_(ABn)).

At a next step 408, which along with steps 410 and 412 are optional, butpreferred, one or more disruptive beat(s) are detected, if present,based on the cumulative values. Steps 408-412 are especially useful ifoptional step 306 was not performed, or if step 306 did not includeremoving easily detected ectopic beats (e.g., identified where a cyclelength of a beat is less than a threshold percentage e.g., 80% of themean cycle length, yet is surrounded by beats having cycle lengths thatare greater than the threshold percentage). Even if easily detectedectopic beats were removed at step 306, steps 408-412 are useful toremove more difficult to detect ectopic beats, or other types ofdisruptive beats.

Disruptive beats, which can include ectopic beats, are caused by anirregularity of heart rate and/or heart rhythm involving extra orskipped beats. More generally, a disruptive beat, as the term is usedherein, is any beat in a series of beats that offsets a regular beatpattern by a non-multiple of N, where N is the number of beats afterwhich the beat pattern repeats. For instance if N=4, and a sequencebegins as A₁B₁C₁D₁A₂B₂C₂D₂ A₃B₃C₃D₃A₄B₄A₅B₅C₅D₅ then the bolded A₄B₄describes two disruptive beats. Many ectopic type disruptive beats mayhave already been removed at step 306, which was discussed above.However, there may be some ectopic beats not identified in the simplealgorithm (i.e., the simple threshold comparison) used in step 306.Further, there are other types of disruptive beats that would not beidentified using the simple algorithm of step 306. Further, since step306 is optional, it is possible that no ectopic beats are removed atstep 306.

If disruptive beats are detected, then they are compensated for at step412, e.g., by removing or replacing the disruptive beats, or byinserting extra beats. The method then returns to step 308, so thatpairwise combinations can be recalculated at step 402, with thedisruptive beats removed, replaced, or extra beats inserted. Ifdisruptive beats A₄B₄ are removed, then beats A₅B₅C₅D₅ become beatsA₄B₄C₄D₄. If disruptive beats are A₄B₄ are replaced, they can bereplaced, e.g., with an average beat set A_(avg)B_(avg)C_(avg)D_(avg),or a beat set equal to the previous beat set (e.g., A₃B₃C₃D₃). If extrabeats are inserted, then extra beats C₄D₄ can be inserted after A₄B₄,e.g., where values for beats C₄D₄ can be an average of previous C and Dvalues (i.e., C₄=avg (C₁+C₂+C₃; and D₄=avg (D₁+D₂+D₃), or equal to the Cand D values from the previous beat set (i.e., C₄=C₃; and D₄=D₃). Theseare just a few examples of how disruptive beats can be compensated forat step 412, which are not meant to be limiting. One of ordinary skillin the art would appreciate from this description that alternatives waysof compensating for disruptive beats are possible, which are also withinthe scope of the present invention. Details of unique ways of detectingdisruptive beats based on cumulative values, in accordance withembodiments of the present invention, are discussed below with referenceto FIGS. 8A and 8B.

At step 414 myocardial mechanical stability is monitored based on thecumulative values. As explained above, this step preferably occurs afterdisruptive beats, if present, are compensated for at steps 408-412. Ifoptional steps 408-412 are not performed, then flow would go directlyfrom step 406 to step 414. In specific embodiments, step 414 includesdetermining, based on the cumulative values, whether mechanicalalternans are present. In other embodiments, step 414 includes trackingchanges in myocardial mechanical stability over time. Step 414 will nowbe described in more detail with reference to FIGS. 6A and 6B and FIGS.7A and 7B.

FIG. 6A is an exemplary graph of cumulative average values whenmechanical alternans are present, and FIG. 6B is an exemplary graph ofcumulative average values when mechanical alternans are not present. Ascan be appreciated from FIGS. 6A and 6B, when mechanical alternans arepresent the cumulative average values remain above a threshold(represented by a dashed line), and when mechanical alternans are notpresent the cumulative average values remain below the threshold.Accordingly, in embodiments where cumulative values (G) are cumulativeaverage values, the presence of mechanical alternans can be determinedby comparing cumulative average values to a threshold. Such a thresholdcan be determined, e.g., through experimentation. The threshold can bespecific to a patient, or specific to a population.

In another embodiment, changes in myocardial mechanical stability can bemonitored by tracking changes in cumulative average values that areobtained from time to time (e.g., once a day, week, month or other timeperiod). For example, if the cumulative average values increase overtime, then it can be determined that the patient's myocardial mechanicalstability is worsening. If the cumulative average values decrease overtime, then it can be determine that the patient's myocardial mechanicalstability is improving.

FIG. 7A is an exemplary graph of cumulative sum values when mechanicalalternans are present, and FIG. 7B is an exemplary graph of cumulativesum values when mechanical alternans are not present. As can beappreciated from FIGS. 7A and 7B, where mechanical alternans are presentthe cumulative sum values continually increase, and where mechanicalalternans are not present the cumulative sum values do not continuallyincrease (but rather, go up and down in a generally random manner).Accordingly, in embodiments where cumulative values (G) are cumulativesum values, the presence of mechanical alternans can be determined,e.g., by comparing a slope of the cumulative sum values to a slopethreshold. Alternatively, it can be determined that mechanical alternansare present when at least a specific number of consecutive cumulativesum values increase in value.

In another embodiment, changes in myocardial mechanical stability can bemonitored by tracking changes in the cumulative sum values that areobtained from time to time (e.g., once a day, week, month or other timeperiod). For example, if the slope of the cumulative sum valuesincreases over time, then it can be determined that the patient'smyocardial mechanical stability is worsening. If the slope of thecumulative sum values decreases over time, then it can be determine thatthe patient's myocardial mechanical stability is improving.

Specific embodiments of the present invention are also directed to themonitoring myocardial mechanical stability based on cumulative values,where a patient's heart is not paced, as well as where N is the integer2.

Detecting Disruptive Beats in the Time Domain

As mentioned above, by using cumulative values, such as cumulativeaverages or cumulative sums, embodiments of the present inventionprovide unique ways in which disruptive beats can be detected. This willnow be described with reference to FIGS. 8A and 8B.

FIG. 8A is an exemplary graph of cumulative average values whenmechanical alternans are present, but a disruptive beat is also present.In this example, a disruptive (e.g., missing or extra) beat can bedetected when the cumulative average values stay consistently within onerange of values and then suddenly shift into another (e.g., lower) rangeof values, e.g., within a few beats or specified short amount of time.For example, if at least X consecutive cumulative average values arewithin a predefined range, followed by at least X further consecutivecumulative average values within a different predefined range, then itcan be determined that a disruptive beat caused the sudden change in therange of cumulative average values. It is the use of cumulativeaveraging of pairwise combinations that enables disruptive beats to bedetected in this manner. The arrow in FIG. 8A shows that the disruptivebeat occurs in 11^(th) set of N beats which was used to determinepairwise combination S₁₁.

FIG. 8B is an exemplary graph of cumulative sum values when mechanicalalternans are present, but a disruptive beat is also present. In thisexample, a disruptive beat can be detected when the cumulative sumvalues consistently increase for a predetermined number of beats oramount of time, and then suddenly consistently decrease for apredetermined number of beats or amount of time. For example, if thereare at least X consecutive cumulative sum values that increase in value,followed by at least X further consecutive cumulative sum values thatdecrease in value, then it can be determined that a disruptive beatcaused the sudden change in cumulative average values. For anotherexample, if the cumulative values have a consistently positive slopefollowed by a consistently negative slope, then it can be determinedthat a disruptive beat caused the sudden change in slope of cumulativevalues. It is the use of cumulative summing of pairwise combinationsthat enable disruptive beats to be detected in this manner. The arrow inFIG. 8B shows that the disruptive beat occurs in 11^(th) set of N beatswhich was used to determine pairwise combination S₁₁.

As was mentioned above in the discussion of step 408 (of FIG. 4), whendisruptive beats are detected they should be compensated for, e.g., byremoving the disruptive beats, replacing the disruptive beats, orinserting additional beats. After they are compensated for, thealgorithm returns to step 308 (of FIG. 3) so that after the disruptivebeats are removed, replaced, or additional beats are inserted, therevised beats (with the disruptive beats removed or replaced, or withbeats added) can be re-divided up into a plurality of sets of N beats.Then, step 310 is repeated, which, as described above, can includerepeating steps 402 through 410 with the revised plurality of sets of Nconsecutive beats.

Where N=4, for example, and it is determined using one of the aboveembodiments that a disruptive beat occurs within certain set of N beats,there need not be a determination of which beat within the N beat set isthe disruptive beat. Rather, a single beat can be removed (or added orreplaced with 2 beats). This causes the shifting all of the followingsets of N beats by one beat when the algorithm returns to step 308,after the disruptive beats are removed or replaced. At that point thebeats (with a disruptive beat, or a beat added) can be re-divided upinto a plurality of sets of N beats, as mentioned above. If it stillappears that a disruptive beat exists (at step 410), then once again asingle beat can be removed (or added or replaced with 2 beats) therebyshifting all of the following sets of N beats by another beat. One ortwo iterations will likely account for all the disruptive beats for theplurality of beats being analyzed at the time.

Frequency Domain Analysis

When frequency domain analysis is being used to determine whether thereis an AB alternans pattern (i.e. an alternans pattern that repeats every2 beats), time domain data is converted to the frequency domain, e.g.,using a Fourier Transformation. Then a magnitude at 0.5 cycles/beat ofthe resulting frequency spectra is analyzed, e.g., by comparing themagnitude to a threshold. Further, if a patient's heart is paced using apatterned pacing sequence that repeats every 2 beats, which may resultin an AB alternans pattern, then the frequency of interest is 0.5cycles/beat. In other words, the frequency of interest to detect analternans pattern that repeats every 2 beats is 0.5 cycles/beat.

As explained in the published Bulling a patent application, which wasincorporated by reference above, if a patient's heart is paced using apatterned pacing sequence that repeats every 3 beats, which may resultin an ABC electrical alternans pattern (i.e. an electrical alternanspattern that repeats every 3 beats), then the frequency of interest is0.33 cycles/beat. Further, if a patient's heart is paced using apatterned pacing sequence that repeats every 4 beats, which may resultin an ABCD electrical alternans pattern (i.e. an electrical alternanspattern that repeats every 4 beats), then the frequency of interest is0.25 cycles/beat. In other words, Bulling a generally explains that whena patient's heart is paced using a patterned pacing sequence thatrepeats every N beats, then 1/N cycles/beat is the frequency of interestto determine whether electrical alternans are present.

When a patient is experiencing an AB alternans pattern (i.e. analternans pattern that repeats every 2 beats), the measured frequencycontent at 0.5 cycles/beat is typically great enough to bedistinguishable from noise. However, when a patient is experiencing anABC alternans pattern (i.e. an alternans pattern that repeats every 3beats), the measured frequency content at 0.33 cycles/beat may not begreat enough to be distinguishable from noise. Further, when patient isexperiencing an ABCD alternans pattern (i.e. an alternans pattern thatrepeats every 4 beats), the measured frequency content at 0.25cycles/beat will even more likely not be great enough to bedistinguishable from noise. Embodiments of the present invention, asdescribed below with reference to FIGS. 9-12, overcome such problems.

FIG. 9 is a high level flow diagram useful for describing embodiments ofthe present invention that relate to monitoring myocardial mechanicalstability at step 310 (of FIG. 3), in the frequency domain, based on theplurality of sets of N consecutive beats produced at step 308 (of FIG.3). When explaining the steps in FIG. 9, it will be assumed again forthe sake of explanation that a patient is paced using a patterned pacingsequence that repeats every 4 beats (i.e., that N=4), and that 1000beats are being analyzed. Thus, it is also assumed that the 1000 beatsare separated into 250 sets of 4 consecutive beats at step 308.

Referring to FIG. 9, at step 902, for each set of N consecutive beats, 2of the N beats are selected to produce a sub-set of 2 beats per set of Nconsecutive beats. Continuing with the example where N=4, at step 902,for each of the 250 sets of 4 consecutive beats, 2 of the 4 beats areselected to produce a sub-set of 2 beats per set of 4 consecutive beats.Were N=4, each set of N (i.e., 4) consecutive beats includes beats A, B,C and D (i.e., a beat pattern ABCD). Thus, at step 402, beats A and B,beats A and C, beats A and D, beats B and C, beats B and D, or beats Cand D can be selected to produce the sub-sets of 2 beats per set of 4consecutive beats. Preferably, the 2 beats selected at step 902 areconsecutive beats (e.g., beats A and B, beats B and C, or beats C andD). A likely 2 beats to select are the first two 2 in the set (i.e.,beats A and B), because it is believed that mechanical alternans aretypically be most noticeable in the first 2 beats of each set.Accordingly, for the following discussion is it will be assumed thatbeats A and B (or simply beats AB) are selected at step 402, resultingin 250 sub-sets (A₁B₁, A₂B₂ . . . A₂₅₀B₂₅₀). However, beats B and C(also simply referred to as beats BC) can be selected at step 402,resulting in 250 sub-sets (B₁C₁, B₂C₂ . . . B₂₅₀C₂₅₀). Similarly, beatsC and D could be selected.

Next, step 904 includes transforming time domain data, associated withthe plurality of sub-sets of 2 beats produced at step 902, to frequencydomain data. This can be accomplished, in accordance with a specificembodiment, by aligning the beats of the sub-sets (produced at step 902)to match in time. For example, assuming the signal indicative ofmechanical functioning of the patient's heart for a plurality ofconsecutive beats is a photoplethysmography (PPG) signal, FIG. 10illustrates aligning beats A₁ and B₁ of sub-set A₁B₁ with beats A₂ andB₂ of sub-set A₂B₂. For simplicity, the AB beats of sub-setsA₃B₃-A₂₅₀B₂₅₀ are not shown. The aligning of beats can be achieved,e.g., by matching the max amplitude for each beat, or by matching otherbeat markers, such as the dichroic notch of each beat in the PPG signal.Next, for a specified region of interest within the beats, theequivalent time points of each beat are grouped together to createensembles of samples, examples of which are shown at 1002 and 1004 inFIG. 10. A Fourier Transform or Fast Fourier Transform (FFT) of eachensemble is taken to view the frequency behavior of the beats. Othertechniques for transforming time domain data to frequency domain datamay be used. FIG. 10 only shows two regions of interest 1002 and 1004for which frequency domain analysis is performed. However, it ispossible to have many alternative and/or additional regions of interest.For example, if each beat is made up of 200 samples, there can be 200regions of interest (one for each time sample) that are analyzed. Then,the region that produces the maximum magnitude of alternans can beconsidered to be the region of interest used for further analysis.

Returning to FIG. 9, at step 906, the frequency content at 0.5cycles/beat is determined, based on the frequency domain data. At step908, myocardial mechanical stability is monitored based on the frequencycontent at 0.5 cycles/beat. What is unique about step 908 is that thefrequency of interest is 0.5 cycles/beat, even though the alternanspattern repeats every N beats, where N is at least 3 (i.e., alwaysgreater than 2). The reason the frequency content of interest is 0.5cycles/beat, in this embodiment, is because only 2 out of the N beatsare being analyzed.

The benefits of the frequency domain embodiments of the presentinvention can be appreciated from the graphs of FIGS. 11 and 12. FIG. 11is an exemplary alternans magnitude versus frequency graph for a patientthat is pacing using a patterned pacing sequence that repeats every 4beats. Using prior art techniques, it is expected that the frequency ofinterest is 0.25 (i.e., ¼ cycles/beat). As can be seen from FIG. 11, thealternans magnitude at 0.25 cycles/beat is about 1.25. It can also beseen that there is an alternans magnitude of about 2.2 at 0.5cycles/beat.

FIG. 12 is an exemplary alternans magnitude versus frequency graph thatwas produced starting with the same time domain data used to produceFIG. 11, but using the embodiment of the present invention describedwith reference to FIG. 9. More specifically, from each 4 beat set (i.e.,from each beat pattern ABCD), the first 2 beats (i.e., the AB beats)were selected at step 902 to produce sub-sets of 2 beats each (A₁B₁,A₂B₂ . . . A₂₅₀B₂₅₀), and then the resulting time domain data wastransformed to the frequency domain. In this embodiment of the presentinvention the frequency of interest is 0.5 cycles/beat, as was describedabove. As can be seen from FIG. 12, the magnitude at 0.5 cycles/beat isabout 3.75, which is three times the 1.25 magnitude at the 0.25cycles/beat frequency of interest in FIG. 11. The alternans magnitude of3.75 at 0.5 cycles/beat in FIG. 12 is also more than 50% greater thanthe alternans magnitude of 2.2 at 0.5 cycles/beat in FIG. 11. Thus, itcan be seen from the graphs of FIGS. 11 and 12 that it is more likelythat alternans will be detected above noise using the frequency domainembodiments of the present invention described with reference to FIG. 9.

A decision as to whether mechanical alternans are present can be made,e.g., by comparing a peak alternans magnitude to a constant threshold,or a threshold that changes with the noise level. For example, thethreshold can be set at a multiple (e.g., 3 times) the mean noise level,where it can be assumed that magnitudes at frequencies prior to thefrequencies of interest are noise. For example, if the frequency ofinterest is 0.5 cycles/beat, it can be assumed that all magnitude ofalternans prior to 0.45 cycles/beat are noise.

In a specific embodiment, magnitudes of alternans are tracked over timeto thereby track how a patients myocardial mechanical stability changesover time. For example, a patient may be paced for a period of time,once per day (or week, or month or other period) using the samepatterned pacing sequence, and a magnitude of alternans can bedetermined at 0.5 cycles/beat each time. If over time the magnitudes ofalternans increase, it can be determined that the patient's myocardialmechanical stability is worsening. If over time the magnitudes ofalternans decrease, it can be determined that the patient's myocardialmechanical stability is improving.

Specific embodiments of the present invention are also directed toperforming the frequency domain analysis described with reference toFIG. 9, where a patient's heart is not paced.

Responses to Detection of Mechanical Alternans

If an embodiment of the present invention is used to determine thatmechanical alternans are present, it can be indicative of heightenedrisk of heart failure. The ICD 10 may be programmed to respond in avariety of ways.

More specifically, one or more response can be triggered at step 312 (ofFIG. 3) if mechanical alternans are determined to be present. Inaccordance with an embodiment of the present invention, informationrelated to the mechanical alternans can be stored. This can include, forexample, storing amplitude, slope, timing, and/or duration informationrelating to the alternans. Such information can be continually, or fromtime to time, automatically uploaded to an external device (e.g., 102).Such an external device can be located, e.g., in the patients' home, andthe information can be transmitted (e.g., through telephone lines or theInternet) to a medical facility where a physician can analyze theinformation. Alternatively, the external device can be located at amedical facility, and the information can be uploaded when the patientvisits the facility.

As mentioned above, mechanical alternans are a known predictor of heartfailure. Accordingly, in an embodiment, a patient is alerted (e.g.,using alert 118) when alternans are detected. Such an alert could be avibratory or auditory alert that originates from within the implantabledevice 10. Alternatively, the implantable device 10 may wirelesslytransmit an alert to an external device that produces a visual orauditory alert that a patient can see or hear. The alert may inform thatpatient that he should rest, or if the patient is operating some type ofdangerous machinery (e.g., a car), that the patient should stop whatthey are doing.

Additionally or alternatively, the patient can be instructed to takemedication when alerted. In still another embodiment, a physician orother person (e.g., a caregiver, guardian or relative of the patient) isalerted whenever the presence of mechanical alternans is detected.

In further embodiments, therapy can be triggered in response todetecting the presence of mechanical alternans. One type of therapywould be for an implanted device (e.g., device 10) to stimulate thepatient's vagus nerve, in an attempt to prevent an arrhythmia fromoccurring. In another embodiment, the implanted device, if appropriatelyequipped, can deliver appropriate drug therapy. In still anotherembodiment, the implanted device, if appropriately equipped, can deliverappropriate resynchronization therapy. These are just a few examples ofthe types of responses that can be performed upon detection ofmechanical alternans. One of ordinary skill in the art would understandfrom the above description that other response are also possible, whilestill being within the spirit and scope of the present invention.

In further embodiments, changes in myocardial mechanical stability aretracked, as described above, and one or more of the above describedresponses occur if the mechanical instability of the myocardium exceedsa corresponding threshold, or mechanical stability of the myocardiumfalls below a corresponding threshold.

While the invention has been described by means of specific embodimentsand applications thereof, it is understood that numerous modificationsand variations could be made thereto by those skilled in the art withoutdeparting from the spirit and scope of the invention. It is therefore tobe understood that within the scope of the claims, the invention may bepracticed otherwise than as specifically described herein.

Example embodiments of the methods, systems, and components of thepresent invention have been described herein. As noted elsewhere, theseexample embodiments have been described for illustrative purposes only,and are not limiting. Other embodiments are possible and are covered bythe invention. Such embodiments will be apparent to persons skilled inthe relevant art(s) based on the teachings contained herein.

Thus, the breadth and scope of the present invention should not belimited by any of the above-described exemplary embodiments, but shouldbe defined only in accordance with the following claims and theirequivalents.

1. In an implantable system, a method for monitoring myocardialmechanical stability based on a signal that is indicative of mechanicalfunctioning of the patient's heart for a plurality of consecutive beats,the method comprising: (a) dividing the plurality of consecutive beatsinto a plurality of sets of N consecutive beats, where N is an integerthat is at least 3; (b) for each set of N consecutive beats, selecting 2of the N beats to produce a sub-set of 2 beats per set of N consecutivebeats; (c) transforming time domain data, associated with the pluralityof sub-sets of 2 beats, to frequency domain data; and (d) monitoringmyocardial mechanical stability based on the frequency domain data. 2.The method of claim 1, wherein the signal is obtained as the patient'sheart is paced for a period of time using a patterned pacing sequencethat repeats every N beats, so that the signal that is indicative ofmechanical functioning of the patient's heart for a plurality ofconsecutive beats while the patient's heart is being paced using thepatterned pacing sequence that repeats every N beats.
 3. The method ofclaim 1, wherein step (d) includes determining, based on the alternansmagnitude at 0.5 cycles/beat, whether mechanical alternans are present.4. The method of claim 1, wherein step (d) includes tracking changes inthe alternans magnitude at 0.5 cycles/beat as steps (a) through (c) arerepeated over time, to thereby track changes in myocardial mechanicalstability.
 5. The method of claim 1, wherein the selecting 2 of the Nbeats, for each set of N consecutive beats at step (d), comprisesselecting 2 consecutive beats from each set of N beats.
 6. The method ofclaim 5, wherein the selecting 2 of the N beats, for each set of Nconsecutive beats at step (c), comprises selecting the first 2 beatsfrom each set of N beats.
 7. The method of claim 1, further comprisinganalyzing the mechanical signal obtained at step (b) to compensate forectopic beats prior to the dividing at step (c).
 8. An implantablesystem for monitoring myocardial mechanical stability based on a signalthat is indicative of mechanical functioning of the patient's heart fora plurality of consecutive beats, the system comprising: one or moresensor to obtain the signal that is indicative of mechanical functioningof the patient's heart for a plurality of consecutive beats; and acontroller to divide the plurality of consecutive beats into a pluralityof sets of N consecutive beats, where N is an integer that is at least3; select 2 of the N beats to produce a sub-set of 2 beats per set of Nconsecutive beats, for each set of N consecutive beats; transform timedomain data, associated with the plurality of sub-sets of 2 beats, tofrequency domain data; and monitor myocardial mechanical stability basedon the frequency domain data.
 9. The system of claim 8, furthercomprising one or more pulse generator to pace the patient's heart for aperiod of time using a patterned pacing sequence that repeats every Nbeats; and wherein the one or more sensor obtains the signal that isindicative of mechanical functioning of the patient's heart for aplurality of consecutive beats while the patient's heart is being pacedusing the patterned pacing pattern that repeats every N beats.
 10. Thesystem of claim 8, wherein the controller determines, based on thefrequency domain data, an alternans magnitude at 0.5 cycles/beat, andmonitors myocardial mechanical stability based on the alternansmagnitude at 0.5 cycles/beat.
 11. The system of claim 10, wherein thecontroller monitors myocardial mechanical stability by determining,based on the alternans magnitude at 0.5 cycle/beat, whether mechanicalalternans are present.
 12. The system of claim 10, wherein thecontroller tracks changes in the alternans magnitude at 0.5 cycles/beatover time, to thereby track changes in myocardial mechanical stability.13. The system of claim 8, wherein the controller selects 2 of the Nbeats, for each set of N consecutive beats, by selecting 2 consecutivebeats from each set of N beats.
 14. The system of claim 13, wherein thecontroller selects 2 of the N beats, for each set of N consecutivebeats, by selecting the first 2 beats from each set of N beats.
 15. Thesystem of claim 8, wherein the controller analyzes the signal tocompensate for ectopic beats prior to dividing the plurality ofconsecutive beats into a plurality of sets of N consecutive beats.